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Publications from the NIA Interventions Testing Program

ITP - Pool

Warner, H. R., Ingram, D., Miller, R. A., Nadon, N. L. and Richardson, A. G. 2000. Meeting Report: Program for testing biological interventions to promote healthy aging. Mechanisms of Aging and Development 115:199-208. [PMID 10906513 ]

Miller, R. A., Harrison, D. E., Astle, C. M., Floyd, R. A., Flurkey, K., Hensley, K. L., Javors, M. A., Leeuwenburgh, C., Nelson, J. F., Ongini, E., Nadon, N. L., Warner, H. R., and Strong, R. 2007. NIA Interventions Testing Program: Study Design and an Interim Report. Aging Cell 6:565-575. [PMID 17578509 . PMC2695675]

Nadon, N. L., Strong, R., Miller, R. A., Nelson, J., Javors, M., Sharp, Z. D., Peralba, J. M. and Harrison, D. E. 2008. Design of Aging Intervention Studies: the NIA Interventions Testing Program. AGE 30:187-199. [AGE online - http://dx.doi.org/10.1007/s11357-008-9048-1 ; NIHMSID47726] [PMID 19424842 ]

Strong, R., Miller, R. A., Astle, C. M., Floyd, R. A., Flurkey K., Hensley, K. L., Javors, M. A., Leeuwenburgh, C., Nelson, J. F., Ongini, E., Nadon, N. L., Warner, H. R., and Harrison, D. E. 2008. Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice. Aging Cell 7:641-650. [PMID 18631321 ]

Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., Pahor, M., Javors, M. A., Fernandez, E. and Miller, R. A. 2009. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460:392-395. [PMID 19587680 ]

Miller, R. A., Harrison, D., Astle, C. M., Baur, J. A., deCabo, R., Fernandez, E., Flurkey, K., Javors, M. A., Nelson, J. F., Pletcher, S., Sharp, Z. D., Sinclair, D., Starnes, J. W., Wilkinson, J. E., Nadon, N. L., Strong, R. 2011. Rapamycin, But Not Resveratrol or Simvastatin, Extends Lifespan of Genetically Heterogeneous Mice. J. Gerontology, Biological Sciences 66A:191-201. [PMID 20974732 ]

Wilkinson, J. E., Burmeister, L., Brooks, S. V., Carames, B., Friedline, S., Harrison, D., Lotz, M., Nadon, N., Strong, R., Wood, L. K., Woodward, M. A., and Miller, R. A. Rapamycin Slows Aging in Mice. 2012. Aging Cell 11:675-682. [PMID: 22587563 ]

Strong, R., Miller, R. A., Astle, C. M., Baur, J. A., de Cabo, R., Fernandez, E., Guo, W., Javors, M., Kirkland, J. L., Nelson, J. F., Sinclair, D., Teter, B., Williams, D., Zaveri, N., Nadon, N. L., Harrison, D. E. 2013. Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium chain triglyceride oil on lifespan of genetically heterogeneous mice. J. Gerontology, Biological Sciences 68:6-16. [PMID 22451473 ]

Wilkinson, J. E., Burmeister, L., Brooks, S. V., Carames, B., Friedline, S., Harrison, D., Lotz, M., Nadon, N., Strong, R., Wood, L. K., Woodward, M. A., and Miller, R. A. Rapamycin Slows Aging in Mice. 2012. Aging Cell 11:675-682. [PMID: 22587563 ]

Miller, R. A., Harrison, D. E., Astle, C. M., Fernandez, E., Flurkey, K., Han, M., Javors, M. A., Li, X., Nadon, N. L., Nelson, J. F., Pletcher, S., Salmon, A. B., Sharp, Z. D., Van Roekel, S., Winkleman, L., Strong, R. Rapamycin-Mediated Lifespan Increase in Mice is Dose and Sex-Dependent and Metabolically Distinct from Dietary Restriction. 2014. Aging Cell 13:468-477. doi: 10.1111/acel.12194. [PMID: 24341993 ]

Harrison D. E., Strong R., Allison, D. B., Ames, B. N., Astle, C. M., Atamna, H., Fernandez, E., Flurkey, K., Javors, M. A., Nadon, N. L., Nelson, J. F., Simpkins, J. W., Smith, D., Wilkinson, J. E., and Miller, R. A. Acarbose, 17-α-Estradiol, and Nordihydroguaiaretic Acid Extend Mouse Lifespan Preferentially in Males. [2014] Aging Cell, 13:273-282. DOI: 10.1111/acel.12170. [PMID: 24245565 ]

Nadon, N. L., R. A. Miller, R. Strong, and D. E. Harrison. NIA Interventions Testing Program: a collaborative approach for investigating interventions to promote healthy aging. Handbook of the Biology of Aging, 8th Edition. Eds: M. R. Kaeberlein and G. M. Martin. Chapter 10, pages 288 - 303, 2015. Academic Press.

Strong, R., Miller, R. A., Antebi, A., Astle, C. M., Bogue, M., Denzel, M. S., Fernandez, E., Flurkey, K., Hamilton, K. L., Lamming, D. W., Javors, M. A., de Magalhães, J. P., McCord, J. M., Miller, B. F., Müller, M., Nelson, J. F., Ndukum, J., Rainger, G. E., Richardson, A., Sabatini, D. M., Salmon, A. B., Simpkins, J. W., Steegenga, W. T., Nadon, N. L., Harrison, D. E. 2016. Longer lifespan in male mice treated with a weakly-estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer. Aging Cell 15:872-84 DOI: 10.1111/acel.12496.

Nadon, N. L., Strong, R., Miller, R. A., Harrison, D. E. 2016. NIA Interventions Testing Program: Investigating putative aging interventions agents in a genetically heterogeneous mouse model. eBioMedicine PII: S2352-3964(16)30554-0. DOI: 10.1016/j.ebiom.2016.11.038. online http://www.sciencedirect.com/science/article/pii/S2352396416305540

ITP - TJL

Pazdro R., Harrison D.E. 2013. Murine adipose tissue-derived stromal cell apoptosis and susceptibility to oxidative stress in vitro are regulated by genetic background. PLoS One. 8: e61235. [PMCID: PMC3617166]

Lamming D.W., Ye L., Astle C.M., Baur J.A., Sabatini D.M., Harrison D.E. 2013. Young and old genetically heterogeneous HET3 mice on a rapamycin diet are glucose intolerant but insulin sensitive. Aging Cell 12:712-18. [PMCID: PMC3727050]

Ye L., Widlund A.L., Sims C.A., Lamming D.W., Guan Y., Davis J.G., Sabatini D.M., Harrison D.E., Vang O., Baur J.A. 2013. Rapamycin doses sufficient to extend lifespan do not compromise muscle mitochondrial content or endurance. Aging 5(7):539-50. [PMCID: PMC3765582]

Zhou Y., Harrison D.E., Love-Myers K., Chen Y., Grider A., Wickwire K., Burgess J.R., Stochelski M.A., Pazdro R. 2014. Genetic Analysis of Tissue Glutathione Concentrations and Redox Balance. Free Radic. Biol. Med. 71:157-64. doi.org/10.1016/j.freeradbiomed.2014.02.027

Chu H.P., Liao Y., Novak J.S., Hu Z., Merkin J.J., Shymkiv Y., Braeckman B.P., Dorovkov M.V., Nguyen A., Clifford P.M., Nagele R.G., Harrison D.E., Ellis R.E., Ryazanov A.G. 2014. Germline Quality Control: eEF2K Stands Guard to Eliminate Defective Oocytes. Dev. Cell. 2014 28:561-72. doi: 10.1016/j. devcel.2014. 01.027

Harrison D.E., Astle C.M., Niazi M.K.K., Major S., Beamer G.L. 2014, Genetically diverse mice are novel and valuable models of age-associated susceptibility to Mycobacterium tuberculosis. Immun. Aging 11:24. doi: 10.1186/s12979-014-0024-6. eCollection [PMID: 25606048]

Yuan R., Gatti E.M.; Krier R., Malay E., Schultz D., Peters L.L., Churchill G.A., Harrison D.E., Paigen B. 2015. Genetic Regulation of Female Sexual Maturation and Longevity Through Circulating IGF1. J. Gerontol. A. Biol. Sci. Med. Sci. 70:817-26; 
 doi: 10.1093/gerona/glu114. Epub 2014 Jul 28. [PMID: 25070661]

Reifsnyder P.C., Doty R., Harrison D.E. 2015. Rapamycin Ameliorates Nephropathy Despite Elevating Hyperglycemia in a Polygenic Mouse Model of Type 2 Diabetes, NONcNZO10/LtJ. PLoS One Dec 4;9(12):e114324. doi: 10.1371/journal.pone.0114324. eCollection 2014. Erratum in: PLoS One. 2015;10(3):e0119748 . [PMID: 25473963]

Gong H., Qian H., Ertl R.P., Astle M.C., Wang G.G., Harrison D.E., Xu X. 2015. P, dietary restriction and rapamycin treatment in mouse brain. Oncotarget 6:15882-90. [PMID: 26021816]

Thompson A.C., Bruss M.D., Price J.C., Khambatta C.F., Holmes W.E., Colangelo M., Dalidd M., Roberts L.S., AstleC.M., Harrison D.E., Hellerstein M.K. 2016. Reduced in vivo proteome replacement rates but not cell proliferation rates predict maximum lifespan extension in mice. Aging Cell15:118-27. doi: 10.1111/acel.12414. Epub 2015 Nov 6. [PMID: 26541492]

Lee B.P., Pilling L.C., Emond F., Flurkey K., Harrison D.E., Yuan R., Peters L.L., Kuchel G.A., Ferrucci L., Melzer D., Harries L.W. 2016. Changes in the expression of splicing factor transcripts and variations in alternative splicing are associated with lifespan in mice and humans . Aging Cell 15:903-13. doi: 10.1111/acel.1

Jiang Z., Harrison D.E., Parsons M.E., McClatchy S., Jacobs L., Pazdro R. 2016. Heritability of in vitro phenotypes exhibited by murine adipose-derived stromal cells. Mamm. Genome 27: 460-468 DOI 10.1007/s00335-016-9655-6

Reifsnyder P.C., Flurkey K., Te A., Harrison D.E., 2016. Rapamycin treatment benefits glucose metabolism in mouse models of type 2 diabetes. Aging 8:3120-3130. doi: 10.18632/aging.101117

Kuchel G.A., Melzer D., Harries L.W. 2017. M icroRNAs miR-203-3p, miR-664-3p and miR-708-5p are associated with median strain lifespan in mice. Nature Sci. Rep. 7:44620. doi: 10.1038/srep44620

Reifsnyder P.C., Ryzhov S., Flurkey K., Anunciado-Koza R.P., Mills I., Harrison D.E., Koza, R.A. 2017. Cardioprotective effects of dietary rapamycin on adult female C57BLKS/J-Leprdb mice. Annals NY Acad. Sci. in press 10-31-17. DOI: 10.1111/nyas.13557

ITP - UM

Steinbaugh, M. J., L. Y. Sun, A. Bartke, and R. A. Miller. 2012. Activation of genes involved in xenobiotic metabolism: a shared signature in mouse models of extended longevity. Am. J. Physiol.— Endocrinology and Metabolism 303: E488 – E495. [PMC3423099]

Hinojosa, C. A., V. E. Mgbemena, S. Friedline, S. N. Austad, R. A. Miller, S. Bose, C. J. Orihuela. 2012. Enteric-delivered rapamycin enhances resistance of aged mice to pneumococcal pneumonia through reduced cellular senescence. Exp. Gerontol. 47:958-965. [PMC3490008]

Lombard, D. B., and R. A. Miller. 2014. Aging, disease and longevity in mice. Ann. Rev. Gerontol. Geriatr. 34: 93 - 138. http://dx.doi.org/10.1891/0198-8794.34.93 .

Pickering, A. M., M. Lehr, and R. A. Miller. 2015. Mouse and primate lifespan is correlated with immunoproteasome expression. J. Clin. Invest. 125:2059-2068. [PMID: 25866968] [PMC4463211]

Ma, S., S. H. Yim, S. G. Lee, E. B. Kim, S.-R. Lee, K.-T. Chang, R. Buffenstein, T. J. Park, R. A. Miller, C B. Clish, V. N. Gladyshev. 2015. Organization of the mammalian metabolome according to organ function, lineage specialization and longevity. Cell Metab. 22:332-343. [PMID: 26244935]

Richardson A., K. E. Fischer, J. R. Speakman, R. de Cabo, S. J. Mitchell, C. A. Peterson, P. Rabinovitch, Y., A. Chiao, G. Taffet, R. A. Miller, R. C. Rentería, J. Bower, D. K. Ingram, W. C. Ladiges, Y. Ikeno, F. Sierra, S. N. Austad. 2016. Measures of healthspan as indices of aging in mice - A recommendation. J. Gerontol. A. Biol. Sci. Med. Sci. 71:427-430. [PMID: 26287941]

Zaseck, L. W., R. A. Miller, and S. V. Brooks. 2016. Rapamycin attenuates age-associated changes in tibialis anterior tendon viscoelastic properties. J. Gerontol. Biol. Sci. doi: 10.1093/gerona/glv307. [PMID: 26809496]

Dominick, G., J. Bowman, X. Li, R. A. Miller and G. Garcia. 2016. mTOR signaling regulates DNA damage response through the CCR4-NOT complex in long-lived Snell Dwarf, GHRKO and PAPPA-KO mice. Aging Cell doi: 10.1111/acel.12525. [PMID: 27618784]

Bajwa, P., P. B. Nagendra, S. Nielsen, A. Bielanowicz, J. M. Lombard, J. E. Wilkinson, M. Serrano, R. A. Miller, P. S. Tanwar. 2016. Age related increase in mTOR activity contributes to the pathological changes in ovarian surface epithelium. 2016. Oncotarget doi: 10.18632/oncotarget.8468. [PMID: 27036037]

Miller, R. A. 2016. Not your father's (or mother's) rodent: moving beyond B6. Neuron dx.doi.org/10.1016/j.neuron.2016.09.009

Lombard, D. B., R. A. Miller, and S. D. Pletcher. 2017. Biology of Aging and Longevity. Hazzard's Geriatric Medicine and Gerontology, 7th Edition. Eds: J. B. Halter, J. G. Ouslander, S. Studenski, K. P. High, S. Asthana, M. A. Supiano, C. Ritchie. Chapter 1, pages 3 - 24. McGraw-Hill, New York.

Berkowitz, B.A., R. A. Miller, and R. Roberts. 2017. Genetically heterogeneous mice show age-related vision deficits not related to increased rod cell L-type calcium channel function in vivo. Neurobiol. Aging 49:198-203. [PMID: 27823846. PMC5154834]

Sadagurski, M., G. Cady, and R. A. Miller. 2017. Anti-aging drugs reduce hypothalamic inflammation in a sex-specific manner. Aging Cell 16:652-660. [PMID: 28544365. PMC5506421]

Bajwa, P., S. Nielsen, J. M. Lombard, L. Rassam, P. Nahar, B. Rueda, J. Erby Wilkinson, R. A. Miller, P. S. Tanwar. 2017. Overactive mTOR signaling leads to endometrial hyperplasia in aged women and mice. Oncotarget 8:7265-7275. [PMID: 27980219. PMC5352319]

Garratt, M., B. Bower, G. G. Garcia, R. A. Miller. 2017. Sex-differences in lifespan-extension with acarbose and 17-α estradiol: gonadal hormones underlie male-specific improvements in glucose tolerance and mTORC2 signaling. Aging Cell 16:1256-1266. doi: 10.1111/acel.12656. [PMID: 28834262. PMC5676051]

Bielas, J. A. Herbst, K. Widjaja, J. Hui, J. M. Aiken, D. McKenzie, R. A. Miller, S. Brooks, J. Wanagat. Long term rapamycin treatment improves mitochondrial DNA quality control in aging mice. Exp.Gerontol., in press.

Garratt, M., K. Lehmann, Y.-M. Tsai, A. Galecki, M. Jain, R. A. Miller. Male lifespan extension with 17-α estradiol is linked to a sex-specific metabolomic response modulated by gonadal hormones in mice. Submitted.

ITP - UT

Majumder S., Caccamo A., Medina D.X., Benavides A.D., Javors M.A., Kraig E., Strong R., Richardson A., Oddo S. 2012. Lifelong rapamycin administration ameliorates age-dependent cognitive deficits by reducing IL-1β and enhancing NMDA signaling. Aging Cell. 11:326-35. doi: 10.1111/j.1474-9726.2011.00791. x. Epub 2012 Feb 1. [PMID: 22212527]

Ramos F.J., Chen S.C., Garelick M.G., Dai D.F., Liao C.Y., Schreiber K.H., MacKay V.L., An E.H., Strong R., Ladiges W.C., Rabinovitch P.S, Kaeberlein M., Kennedy B.K. 2012. Rapamycin reverses elevated mTORC1 signaling in lamin A/C-deficient mice, rescues cardiac and skeletal muscle function, and extends survival. Sci. Transl. Med. 4:144ra103. doi: 10.1126/scitranslmed.3003802. [PMID: 22837538]

Halloran J., Hussong S.A., Burbank R., Podlutskaya N., Fischer K.E., Sloane L.B., Austad S.N., Strong R., Richardson A., Hart M.J., Galvan V. 2012. Chronic inhibition of mammalian target of rapamycin by rapamycin modulates cognitive and non-cognitive components of behavior throughout lifespan in mice. Neuroscience. 223:102-13. doi: 10.1016/j.neuroscience.2012.06.054. Epub 2012 Jun 28. [PMID: 22750207]

Livi C.B., Hardman R.L., Christy B.A., Dodds S.G., Jones D., Williams C., Strong R., Bokov A., Javors M.A., Ikeno Y., Hubbard G., Hasty P., Sharp Z.D. 2013. Rapamycin extends life span of Rb1+/- mice by inhibiting neuroendocrine tumors. Aging 5:100-10. [PMID: 23454836]

Lin A.L., Zheng W., Halloran J.J., Burbank R.R., Hussong S.A., Hart M.J., Javors M., Shih Y.Y., Muir E., Solano Fonseca R., Strong R., Richardson A.G., Lechleiter J.D., Fox P.T., Galvan V. 2013. Chronic rapamycin restores brain vascular integrity and function through NO synthase activation and improves memory in symptomatic mice modeling Alzheimer's disease. J. Cereb. Blood Flow Metab. 33:1412-21. doi: 10.1038/jcbfm.2013.82. Epub 2013 Jun 26. [PMID: 23801246]

Flynn J.M., O'Leary M.N., Zambataro C.A., Academia E.C., Presley M.P., Garrett B.J., Zykovich A., Mooney S.D., Strong R., Rosen C.J., Kapahi P., Nelson M.D., Kennedy B.K., Melov S. 2013. Late-life rapamycin treatment reverses age-related heart dysfunction. Aging Cell. 12:851-62. doi: 10.1111/acel.12109. Epub 2013 Jul 7. [PMID: 23734717]

Hasty P., Livi C.B., Dodds S.G., Jones D., Strong R., Javors M., Fischer K.E., Sloane L, Murthy K., Hubbard G., Sun L., Hurez V., Curiel T.J., Sharp Z.D. 2014. eRapa restores a normal life span in a FAP mouse model. Cancer Prev. Res. 7(1):169-78. doi: 10.1158/1940-6207.CAPR-13-0299. Epub 2013 Nov [PMID: 24282255]

Liu Y., Diaz V., Fernandez E., Strong R., Ye L., Baur J.A., Lamming D.W., Richardson A., Salmon A.B. 2014. Rapamycin-induced metabolic defects are reversible in both lean and obese mice. Aging 6:742-54. [PMID: 25324470]

Rodriguez K.A., Dodds S.G., Strong R., Galvan V., Sharp Z.D., Buffenstein R. 2014. Divergent tissue and sex effects of rapamycin on the proteasome-chaperone network of old mice. Front. Mol. Neuroscience 7:83. doi: 10.3389/fnmol.2014.00083. eCollection 2014. [PMID: 25414638]

Tardif S., Ross C., Bergman P., Fernandez E., Javors M., Salmon A., Spross J., Strong R., Richardson A. 2015. Testing efficacy of administration of the antiaging drug rapamycin in a nonhuman primate, the common marmoset. J. Gerontol. A Biol. Sci. Med. Sci. 70:577-87. doi: 10.1093/gerona/glu101. Epub 2014 Jul 19. [PMID: 25038772]

Bai X., Wey M.C., Fernandez E., Hart M.J., Gelfond J., Bokov A.F., Rani S., Strong R. 2015. Rapamycin improves motor function, reduces 4-hydroxynonenal adducted protein in brain, and attenuates synaptic injury in a mouse model of synucleinopathy. Pathobiol Aging Age Relat. Dis.5:28743. doi: 10.3402/pba. v5.28743. [PMID: 26306821. Free PMC Article]

Ross C., Salmon A., Strong R., Fernandez E., Javors M., Richardson A., Tardif S. 2015. Metabolic consequences of long-term rapamycin exposure on common marmoset monkeys (Callithrix jacchus). Aging (Albany NY). 2015 Nov;7(11):964-73. [PMID: 26568298]

Dodds S.G., Livi C.B., Parihar M., Hsu H.K., Benavides A.D., Morris J., Javors M., Strong R., Christy B., Hasty P., Sharp Z.D. 2016. Adaptations to chronic rapamycin in mice. Pathobiol. Aging Age Relat. Dis. 6:31688. doi: 10.3402/pba.v6.31688. eCollection 2016. [PMID: 27237224]